This proposal is concerned with (1) identification of the component(s) of the phospholipid fraction of hepatic microsomes responsible for the inhibition of drug metabolism, (2) the nature of this inhibition, (3) the interrelationship between the inhibition of drug metabolism and other metabolic events in microsomes, and (4) the influence on drug metabolism of unsaturated fatty acids added to a nutritionally adequate diet. Preliminary results suggest that a phospholipid component of microsomes containing unsaturated fatty acids is responsible for the inhibition of drug metabolism observed in vitro, and that this inhibitory lipid is present in greater quantities in the liver of the neonatal rat. It is the goal of this proposal to delineate the factors, particularly lipoidal in nature, that may be responsible for altered drug metabolism in the neonate as well as in animals of the other extreme of the age spectrum.